Ivonescimab (PD-1×VEGF bispecific) + pemetrexed/carboplatin extends OS after EGFR-TKI in NSCLC

Ivonescimab is a bispecific antibody that simultaneously targets PD-1 (checkpoint inhibition) and VEGF (anti-angiogenesis), aiming to pair immunotherapy with VEGF-pathway blockade in EGFR-variant nonsquamous NSCLC. In the randomized, double-blind Phase 3 HARMONi-A trial in China (NCT05184712), patients with locally advanced/metastatic disease progressing after prior EGFR-TKI were assigned to ivonescimab 20mg/kg or placebo plus pemetrexed/carboplatin for 4 cycles followed by maintenance (n=322; 1:1). At the April 12, 2025 data cutoff (median follow-up 32.5 months), median OS was 16.8 vs 14.1 months (HR 0.74, 95% CI 0.58–0.95; p=0.02) with a 30-month OS rate of 29.1% vs 18.4%; grade ≥3 TEAEs were higher with ivonescimab (67.1% vs 54.7%)—a tradeoff that looks directionally consistent with adding an anti-VEGF/IO component vs chemo alone, where post-TKI outcomes are typically in the low-to-mid teens for median OS depending on subsequent therapies.